Cross-talk between group IIA-phospholipase A(2) and inducible NO-synthase in rat renal mesangial cells

1 Features of glomerulonephritis are expression of the inducible form of NO synthase (iNOS) as well as expression of the secretory group IIA-phospholi pase A(2) (sPLA(2)) in mesangial cells. Interleukin 1 beta (IL-1 beta) indu ces both enzymes with a similar time course resulting in an increase in nit rite production and sPLA(2)-IIA activity. In this study we investigated the relationship between the formation of NO and sPLA(2)-IIA induction in rat renal mesangial cells. 2 Incubation of mesangial cells with the NO-donor, spermine-NONOate, for 24 h induced sPLA(2)-IIA mRNA expression and activity, whereas S-nitroso glut athione alone had only a small stimulatory effect. Stimulation of cells wit h IL-IB caused a marked increase in sPLA(2)-IIA mRNA and activity that were potentiated 3 fold by both NO donors. 3 Coincubation of cells with IL-1 beta and the NOS inhibitor, L-N-G monomet hylarginine (L-NMMA), caused a dose-dependent inhibition of cytokine-induce d sPLA(2)-IIA mRNA expression and activity. 4 sPLA(2)-IIA activity was not stimulated by 8-bromo-cyclic GMP indicating that NO-induced sPLA(2)-IIA induction is independent of cyclic GMP-mediated signal transduction. 5 These data show that NO contributes to the expression by cytokines of sPL A(2)-IIA and establishes a novel type of interaction between iNOS and sPLA( 2)-IIA in mesangial cells. This cross-talk between inflammatory mediators m ay help to promote and sustain an inflammatory state in the kidney.